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A Study of Dostarlimab in Untreated dMMR/MSI-H Locally Advanced Rectal Cancer (AZUR-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05723562
Recruitment Status : Recruiting
First Posted : February 10, 2023
Last Update Posted : February 20, 2024
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
The purpose of this study is to investigate dostarlimab monotherapy in participants with locally advanced Mismatch-repair deficient (dMMR)/Microsatellite instability-high (MSI-H) rectal cancer who have received no prior treatment. Participants who achieve complete clinical response (cCR) following dostarlimab treatment will undergo non-operative management (NOM), including close surveillance for recurrent disease. The goal of the study is to determine if Dostarlimab therapy alone is an effective treatment that can allow participants to avoid chemotherapy, radiation, and surgery.

Condition or disease Intervention/treatment Phase
Neoplasms, Rectal Biological: Dostarlimab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Single-Arm, Open-Label Study With Dostarlimab Monotherapy in Participants With Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer
Actual Study Start Date : April 3, 2023
Estimated Primary Completion Date : November 2, 2026
Estimated Study Completion Date : October 11, 2029

Resource links provided by the National Library of Medicine

Drug Information available for: Dostarlimab

Arm Intervention/treatment
Experimental: Dostarlimab monotherapy Biological: Dostarlimab
Dostarlimab will be administered.
Other Names:
  • JEMPERLI
  • dostarlimab-gxly
  • TSR-042
  • GSK4057190A




Primary Outcome Measures :
  1. Number of Participants with Sustained Complete Clinical Response for 12 Months (cCR12) as assessed by Independent Central Review (ICR) [ Time Frame: 18 Months ]
    cCR12 is achieved when a participant maintains complete clinical response (cCR) as assessed by ICR for 12 months following their post-intervention disease assessment (PIDA)


Secondary Outcome Measures :
  1. Number of Participants with Sustained Complete Clinical Response for 24 Months (cCR24) as assessed by ICR [ Time Frame: 30 Months ]
    cCR24 is achieved when a participant maintains complete clinical response (cCR) as assessed by ICR for 24 months following their post-Intervention disease assessment (PIDA)

  2. Number of Participants with Sustained Complete Clinical Response for 36 Months (cCR36) as assessed by ICR [ Time Frame: 42 Months ]
    cCR36 is achieved when a participant maintains complete clinical response (cCR) as assessed by ICR for 36 months following their post-Intervention disease assessment (PIDA)

  3. Number of Participants with Event Free Survival at 3 years (EFS3) as assessed by Investigator [ Time Frame: 3 years ]
    EFS3 is defined as participants who remained alive and free of disease progression precluding surgery, local recurrence, and distant recurrence at 3 years as assessed by Investigator

  4. Event Free Survival (EFS) as assessed by Investigator [ Time Frame: Up to 74 months ]
    EFS is defined as time from the date of first dose of study intervention to any of the following events: progression of disease that precludes surgery, local recurrence, distant recurrence (all as assessed by the investigator), or death due to any cause

  5. Number of Participants with cCR12 as assessed by Investigator [ Time Frame: 18 Months ]
    cCR12 is achieved when a participant maintains complete clinical response (cCR) as assessed by Investigator for 12 months following their post-intervention disease assessment (PIDA)

  6. Number of Participants with cCR24 as assessed by Investigator [ Time Frame: 30 Months ]
    cCR24 is achieved when a participant maintains complete clinical response (cCR) as assessed by Investigator for 24 months following their post-intervention disease assessment (PIDA)

  7. Number of Participants with cCR36 as assessed by Investigator [ Time Frame: 42 Months ]
    cCR36 is achieved when a participant maintains complete clinical response (cCR) as assessed by Investigator for 36 months following their post-intervention disease assessment (PIDA)

  8. Objective Response Rate (ORR) assessed by ICR [ Time Frame: Up to 33 Weeks ]
    ORR is defined as number of participants achieving a partial response (PR), near complete response (nCR) or complete clinical response (cCR) at PIDA or at least 4 weeks but no longer than 8 weeks after PIDA for participants with nCR or incomplete clinical response (iCR) (PIDA 2) as assessed by ICR

  9. Objective Response Rate (ORR) as assessed by Investigator [ Time Frame: Up to 33 Weeks ]
    ORR by Investigator, defined as achieving a PR, nCR, or cCR at PIDA or at least 4 weeks but no longer than 8 weeks after PIDA for participants with nCR or iCR

  10. Organ Preservation Rate [ Time Frame: 3 years ]
    Organ Preservation Rate defined as not undergoing Total Mesorectal Excision (TME), either as primary management or for local recurrence, or who did not have a permanent colostomy created, at any time up to 3 years

  11. Disease-Specific Survival (DSS) [ Time Frame: Up to 74 months ]
    DSS is defined as time from the date of first dose of study intervention to death due to disease

  12. Disease-Specific Response at 5 years (DSS5) [ Time Frame: Up to 5 years ]
    DSS5 is defined as the number of participants not dying due to disease under study at 5 years from the first dose of study intervention

  13. Overall Survival (OS) [ Time Frame: Up to 74 months ]
    OS is defined as time from first dose of study intervention to death from any cause

  14. Overall Survival at 5 years (OS5) [ Time Frame: Up to 5 years ]
    OS is defined as number of participants as being alive at 5 years from first dose of study intervention

  15. Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), Immune related Adverse Events (irAEs) based on Severity [ Time Frame: Up to 74 months ]
  16. Number of Participants with discontinuation of study intervention [ Time Frame: Up to 24 weeks ]
  17. Serum concentration of Dostarlimab [ Time Frame: Up to 37 weeks ]
  18. Concentration at the end of infusion (C-EOI) of Dostarlimab [ Time Frame: Up to 37 weeks ]
  19. Trough Concentration (C-trough) of Dostarlimab [ Time Frame: Up to 37 weeks ]
  20. Number of Participants with Anti-Drug Antibodies against Dostarlimab [ Time Frame: Up to 37 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+), locally advanced rectal cancer
  • Participant has radiologically and endoscopically evaluable disease.
  • Participant has a tumor which can be categorized as dMMR or MSI-H by local or central assessment

Exclusion Criteria:

  • Participant has distant metastatic disease.
  • Participant has received prior radiation therapy, systemic therapy, or surgery for management of rectal cancer.
  • Participant has any history of interstitial lung disease or pneumonitis
  • Participant has experienced any of the following with prior immunotherapy: any irAE of Grade ≥3, immune-related severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson Syndrome, toxic epidermal necrolysis, or DRESS syndrome), or myocarditis of any grade. Non clinically significant laboratory abnormalities are not exclusionary.
  • Participant has a known additional malignancy that progressed or required active treatment within the past 2 years. Exceptions include adequately treated superficial skin cancers, superficial bladder cancers, and other in situ cancers.
  • Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Participant has a history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies, fusion proteins, or has known allergies to dostarlimab or its excipients.
  • Has received or plans to receive an organ or stem cell transplant that uses donor stem cells (allogeneic stem cell transplant).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05723562


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
Show Show 62 study locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT05723562    
Other Study ID Numbers: 219369
2022-003289-18 ( EudraCT Number )
First Posted: February 10, 2023    Key Record Dates
Last Update Posted: February 20, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
URL: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
JEMPERLI
dostarlimab-gxly
GSK4057190A
Stage II/III rectal cancer
Neoadjuvant
dMMR
MSI-H
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Dostarlimab
Antineoplastic Agents